BDMN is a key intermediate in the synthesis of nitric oxide (NO)-releasing NSAIDs, i.e. non-steroidal anti-inflammatory drugs which release nitric oxide. NO-NSAIDs have antipyretic and anti-inflammatory activities, but lower gastrointestinal toxicity than other non-steroidal anti-inflammatory medicaments. Examples of NO-NSAIDs are NO-acetylsalicylic acid, NO-diclofenac, NO-naproxen, NO-ketoprofen and NO-ibuprofen. The preparation of NO-naproxen is described, for example, in WO 01/10814.
The industrial production of BDMN by reduction or hydrolysis from BDDN, is problematic and poorly selective, as the synthesis of BDDN involves problems concerning production, storage and transport similar to those connected with the use of nitroglycerin.
Mono-nitration of BD with the methods available to date is also problematic and poorly selective on an industrial scale, as dangerous decomposition reactions easily occur when a strong oxidizer (nitric acid) is contacted with an unstable substrate.
Moreover, BDMN obtained by mono-nitration of BD has to be separated from unreacted BDDN and BD. Such separation is, however, potentially dangerous, in that BDMN has, like BDDN, explosive characteristics, therefore neither crystallization nor distillation techniques can be employed. In fact, both BDMN and BDDN are liquid at room temperature and they can decompose upon crystallization due to friction or impaction. Analogously, distillation involves evident hazards owing to the recovery of the explosive compound in the pure form. In view of their chemical-physical characteristics, distillation of a mixture containing BDDN and BDMN would require heating to a temperature at which spontaneous, explosive decomposition could take place.
There is therefore need for a process for the purification of BDMN from BD and BDDN which avoids crystallization or distillation.